Studies in this laboratory are designed to elucidate the role of DNA repair processes in human diseases, carcinogenesis, and aging. Most studies have been conducted with cells from patients with xeroderma pigmentosum (XP), all of whom have defective DNA repair plus the clinical abnormalities of premature aging of the skin and cutaneous malignancies. We measure the DNA excision repair process by assays of UV-induced unscheduled DNA synthesis. We assess the biological effectiveness of DNA repair with assays of post-irradiation colony-forming ability and trypan blue exclusion and have found a striking correlation between the level of effectiveness of DNA repair in XP and the severity of XP-associated neurological abnormalities. We have studied the relationship of UV-induced sister chromatid exchanges to the repair defects of XP. We are extending our work to include cells from patients with other diseases in which DNA repair defects are claimed or suspected, such as Cockayne's syndrome, ataxia telangiectasia, Fanconi's anemia, Werner's syndrome, Rothmund Thompson syndrome and progeria. We have established lymphocyte cell lines (long-term lymphoblast lines) from all six genetic forms of XP. These lines are useful in radiation-sensitivity and biochemical tests.